Buyang Huanwu decoction promotes angiogenesis after cerebral ischemia through modulating caveolin-1-mediated exosome MALAT1/YAP1/HIF-1α axis.

BACKGROUND: Angiogenesis is an effective method for promoting neurological function recovery after cerebral ischemia (CI). Buyang Huanwu decoction (BHD) is a traditional Chinese medicinal recipe that is frequently employed for CI treatment. Previous investigations have validated that it promotes angiogenesis following CI. Nevertheless, the precise mechanism by which it does this has yet to be completely understood. OBJECTIVE: This study aims to examine the underlying mechanism through which BHD facilitates angiogenesis following CI by regulating the exosomal MALAT1/YAP1/HIF-1α signaling axis, specifically via the involvement of caveolin-1 (Cav1), an endocytosis-associated protein. METHODS: A CI model was created using middle cerebral artery occlusion (MCAO). Following the administration of multiple doses of BHD, various parameters, including the neurobehavioral score, pathological damage, and angiogenesis, were assessed in each group of mice to identify the optimal dosage of BHD for treating CI. The molecular processes underlying the angiogenic implications of BHD following CI were investigated exhaustively by employing single-cell sequencing. Finally, the involvement of Cav1 was confirmed in Cav1 knockout mice and Cav1-silenced stably transfected strains to validate the mechanism by which BHD increases angiogenesis following CI. RESULTS: BHD could promote angiogenesis after CI. Single-cell sequencing results suggested that its potential mechanism of action might be connected with Cav1 and the exosomal MALAT1/YAP1/HIF-1α signaling axis. BHD could promote angiogenesis after CI by regulating the exosomal MALAT1/YAP1/HIF-1α axis through Cav1, as validated in vivo and in vitro experiments. Accordingly, Cav1 may be a key target of BHD in promoting angiogenesis after CI. CONCLUSION: This investigation represents the initial attempt to comprehensively ascertain the underlying mechanism of action of BHD in treating CI using single-cell sequencing, gene-knockout mice, and stable transfected cell lines, potentially associated with the modulation of the exosomal MALAT1/YAP1/HIF-1α axis by Cav1. Our findings offer novel empirical evidence for unraveling the regulatory pathways through which Cav1 participates in angiogenesis following CI and shed light on the potential mechanisms of BHD.

Integrating network pharmacology and bioinformatics to explore and experimentally verify the regulatory effect of Buyang Huanwu decoction on glycolysis and angiogenesis after cerebral infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Promoting the recovery of cerebral blood circulation after cerebral infarction (CI) is an important intervention. Buyang Huanwu decoction (BHD) is a classic prescription for treating CI that promotes angiogenesis. Cytoplasmic glycolysis ischaemic-region cells after CI may be highly activated to maintain metabolic activity under hypoxia. From the perspective of long-term maintenance of glycolytic metabolism in the ischaemic area after CI, it may be beneficial to promote angiogenesis and maintain glial cell activation and neuronal survival. In this context, the regulatory relationship of lncRNAs and miRNAs with mRNAs is worthy of attention. Mining the competitive binding relationships among RNAs will aid in the screening of key gene targets post-CI. In this study, network pharmacology and bioinformatics were used to construct a ceRNA network, screen key targets, and explore the effect of glycolysis on angiogenesis during BHD-mediated CI regulation. AIM OF THE STUDY: This study aimed to explore the effect of BHD on angiogenesis after glycolysis regulation in CI. MATERIALS AND METHODS: According to the 21 active BHD ingredients we identified by our research team, we conducted network pharmacology. BHD targets that can regulate glycolysis and angiogenesis after CI were screened from the GeneCards, CTD and OMIM databases. We retrieved CI-related datasets from the GEO database and screened for differentially expressed lncRNAs and miRNAs. LncRNA‒miRNA-mRNA/TF targeting relationships were screened and organized with the miRcode, miRDB, TargetScan, miRWalk, and TransmiR v2.0 databases. Cytoscape was used to construct an lncRNA‒miRNA-mRNA/TF ceRNA network. Through BioGPS, key mRNAs/TFs in the network were screened for enrichment analysis. Animal experiments were then conducted to validate some key mRNAs/TFs and enriched signalling pathways. RESULTS: PFKFB3 and other genes may help regulate glycolysis and angiogenesis through AMPK and other signalling pathways. The anti-CI effect of BHD may involve maintaining activation of genes such as AMPK and PFKFB3 in the ischaemic cortex, maintaining moderate glycolysis levels in brain tissue, and promoting angiogenesis. CONCLUSION: BHD can regulate glycolysis and promote angiogenesis after CI through multiple pathways and targets, in which AMPK signalling pathway activation may be important.

Expression of Tim-3/Galectin-9 pathway and CD8+T cells and related factors in patients with cystic echinococcosis.

OBJECTIVE: One of the primary reasons for the successful patriotization of Echinococcus multilocularis in patients is its ability to induce host immune tolerance. This study examined the expression of the immunosuppressive Tim-3/Galectin-9 pathway, CD8+T cells, and related factors in AE patients. The aim was to analyze the relationship between the Tim-3/Galectin-9 pathway and CD8+T cells in this disease and further understand the mechanism of immune tolerance induced by cystic echinococcosis. METHODS: Using flow cytometry, we evaluated the expression of CTL, CD8+CD28-T cells, CD8+CD28 + IFN-γ + T cells, CD8+CD28+perforin + T cells, CD8+CD28+granzyme B + T cells, CD8+CD28-IL-10 + T cells, CD8+CD28-TGF-ß+T cells, and Tim-3 expression on CD8+T cells in the peripheral blood of control (n = 30) and AE patients (n = 33). qRT-PCR was used to measure CD107a and Tim-3/Galectin-9 mRNA levels in PBMCs from the control and AE groups. Immunohistochemistry was employed to detect IL-10, TGF-ß, and Tim-3/Galectin-9 expressions in the infected livers of AE patients. RESULTS: AE patients exhibited a significant decrease in peripheral blood CTL ratio (P < 0.001) and an increase in CD8+CD28+IFN-γ+T cell ratio (P < 0.001). No significant changes were observed in the ratios of CD8+CD28+perforin + T cells (P = 0.720) and CD8+CD28+granzyme B + T cells (P = 0.051). The proportions of CD8+CD28-T cells (P < 0.001), CD8+CD28-IL-10 + T cells (P < 0.001), and CD8+CD28-TGF-ß+T cells (P < 0.001) were notably higher than in the control group. The expression of Tim-3 on CTL and CD8+CD28-T cells in AE patients was significantly upregulated (P < 0.001, P < 0.001). AE patients displayed a substantial decrease in peripheral blood PBMC CD107a mRNA levels (P < 0.001) and significant elevations in Tim-3/Galectin-9 mRNA levels (P < 0.001, P < 0.001). A negative correlation was observed between CD107a mRNA levels and both Tim-3 (r^2 = 0.411, P < 0.001) and Galectin-9 (r2 = 0.180, P = 0.019) mRNA levels. Expressions of IL-10 (P < 0.001), TGF-ß (P < 0.001), and Tim-3/Galectin-9 (P < 0.001, P < 0.001) in AE patient-infected livers were significantly higher than in uninfected regions. IL-10 and TGF-ß expressions showed a positive correlation with Tim-3/Galectin-9. CONCLUSION: This study suggests that the high expression of Tim-3 on CD8+T cell surfaces in AE patients might promote an increase in CD8+CD28-T cells and related factors, while suppressing CTL and related factor expressions. This potentially induces the onset of immune tolerance, which is unfavorable for the clearance of Echinococcus multilocularis in patients, leading to the exacerbation of persistent infections.

C18ORF54 promotes immune infiltration and poor prognosis as a potential biomarker for hepatocellular carcinoma.

OBJECTIVE: The morbidity of hepatocellular carcinoma (HCC) is increasing annually. The aim of this study is to investigate the molecular mechanisms of upregulated genes in HCC using bioinformatic methods, so as to identify new potential biological markers. METHODS: The Gene Expression Omnibus database (GEO database) was mined for HCC datasets, which were screened for hub genes and subjected to (Gene Ontology) GO and (Kyoto Encyclopedia of Genes and Genomes) KEGG enrichment analysis. The hub genes were analyzed in terms of Receiver Operating Characteristic (ROC) and methylation levels. Validation of hub genes was completed through basic pathological alterations based on the protein and gene expression level of hub genes. The correlation of genes with immune infiltration in HCC was analyzed based on the database Timer 2.0, and the prognosis as well as survival of hub genes in HCC was analyzed using R studio software. Finally, we performed a gene combination drug analysis on the potential therapeutic targets in HCC. RESULTS: Expression-up-regulated genes were screened via differential analysis, which were mainly enriched in cell cycles and DNA replication pathways. Five hub genes, BRCA1 associated RING domain 1 (BARD1), Mismatch Repair Protein (MSH2), Recombinant H2A Histone Family, Member X (H2AFX), Recombinant H2A Histone Family, Member z (H2AFZ) and Chromosome 18 Open Reading Frame 54 (C18orf54) were identified using a Protein-Protein Interaction Networks (PPI). After a comprehensive analysis of ROC curves and methylation gene mutation sites, C18orf54 was localized followed by basic experiments, so as to verify the C18orf54 upregulated in HCC. Based on the online database Timer 2.0, the immune infiltration of C18orf54 gene in HCC was analyzed, which was found to be negatively correlated with CD4+ T cells and macrophages in HCC, meanwhile a further refinement of the immune checkpoint correlation analysis revealed that C18orf54 was mainly correlated with Hepatitis A virus cellular receptor 2 (HAVCR2), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and Cytotoxic T lymphocyte associate protein-4 (CTLA4). The prognosis and survival of patients with HCC expressing C18orf54 were also analyzed, and it was found that such patients had a higher incidence of adjacent liver tissue inflammation, a higher child-Pugh grade score and a higher rate of residual tumor recurrence. Similarly, the prognosis was worse in the subset of patients with C18orf54. Finally, we performed a combined genetic analysis, which suggested that cyclosporine, quercetin, testosterone and calcitriol might be effective in reducing C18orf54 mRNA expression. CONCLUSION: C18orf54 is involved in the immune infiltration and promotes the poor prognosis of HCC, which could be a candidate biomarker for HCC.

Predictive value of C-reactive protein, procalcitonin, and interleukin-6 on 30-day mortality in patients with bloodstream infections / Valor predictivo de la proteína C reactiva, procalcitonina e interleucina-6 en la mortalidad a los 30 días en pacientes con infecciones del torrente sanguíneo

Background We aimed to assess the predictive performance of C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6) at different times points of bloodstream infections (BSI) management. Methods The cases were collected from January 2020 to June 2021 in the First Affiliated Hospital of Xinjiang Medical University (n=185). We collected patients’ records of hsCRP, PCT, and IL-6 serum levels and calculated the clearance of these biomarkers on day 1, day 3, and day 5 (hsCRP-1, hsCRP-3, hsCRP-5, so do PCT, and IL-6). We analyzed these predictive performances for 30-day mortality with ROC and Logistic regression. The correlation between biomarkers and their clearance rates was performed by a rank correlation method. Results The 30-day mortality was 11.35% (21/185). Serial serum hsCRP-3, IL-6-3, PCT-1, PCT-3, and PCT-5 were statistically higher in BSI mortality than survivors. Significant predictive ability was found for 30-day mortality with blood culture (BC) reported fungi (OR, 0.033; 95% CI: 0.002–0.535) and PCT-5 (OR, 1.045; 95% CI: 1.013–1.078) levels, respectively. The AUC of PCT-5 levels for 30-day mortality was 0.784 (95% CI 0.678–0.949), and the cut-off value was 5.455ng/mL. Conclusions PCT-5 is more valuable for the prognosis of 30-day mortality in patients with BSI compared to the other inflammatory biomarkers (AU)

Antecedentes Nuestro objetivo fue evaluar el rendimiento predictivo de la proteína C reactiva (hsCRP), procalcitonina (PCT) e interleucina-6 (IL-6) en distintos momentos del tratamiento de pacientes con infecciones del torrente sanguíneo. Métodos Los casos se recogieron entre enero de 2020 y junio de 2021 en el Primer Hospital Afiliado de la Universidad Médica de Xinjiang (n = 185). Los valores de los niveles séricos de hsCRP, PCT e IL-6 se obtuvieron de los registros de los pacientes y calculamos la depuración de estos biomarcadores en el día 1, el día 3 y el día 5 (hsCRP-1, hsCRP-3, hsCRP-5, PCT e IL-6). Analizamos estos rendimientos predictivos para la mortalidad a 30 días con ROC y regresión logística. La correlación entre los biomarcadores y sus tasas de eliminación se realizó mediante un método de correlación de rangos. Resultados La mortalidad a 30 días fue de 11,35% (21/185). Los valores séricos seriados de hsCRP-3, IL-6-3, PCT-1, PCT-3 y PCT-5 fueron estadísticamente más elevados en los pacientes fallecidos de infecciones del torrente sanguíneo que en los supervivientes. Se halló una capacidad predictiva significativa para la mortalidad por hongos (OR, 0,033; IC 95%: 0,002-0,535) y el valor de PCT-5 (OR, 1.045; IC 95%: 1.013-1.078), respectivamente. El AUC de los niveles de PCT-5 para la mortalidad a 30 días fue de 0,784 (IC 95%: 0,678-0,949), y el valor de corte fue de 5.455 ng/mL. Conclusiones La PCT-5 fue un parámetro de más valor para el pronóstico de mortalidad a 30 días en pacientes con infecciones del torrente sanguíneo en comparación con los demás biomarcadores inflamatorios (AU)

Buyang Huanwu Decoction alleviates cerebral ischemic injury through modulating caveolin-1-mediated mitochondrial quality control.

Introduction: Mitochondrial quality control (MQC) is an important mechanism of neural repair after cerebral ischemia (CI). Recent studies have shown that caveolin-1 (Cav-1) is an important signaling molecule in the process of CI injury, but its mechanism of regulating MQC after CI is still unclear. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine formula that is often used to treat CI. Unfortunately, its mechanism of action is still obscure. Methods: In this study, we tested the hypothesis that BHD can regulate MQC through Cav-1 and exert an anti-cerebral ischemia injury effect. We used Cav-1 knockout mice and their homologous wild-type mice, replicated middle cerebral artery occlusion (MCAO) model and BHD intervention. Neurobehavioral scores and pathological detection were used to evaluate neurological function and neuron damage, transmission electron microscopy and enzymology detection of mitochondrial damage. Finally, western blot and RT-qPCR expression of MQC-related molecules were tested. Results: After CI, mice showed neurologic impairment, neuronal damage, and significant destruction of mitochondrial morphology and function, and MQC was imbalanced. Cav-1 deletion aggravated the damage to neurological function, neurons, mitochondrial morphology and mitochondrial function after CI, aggravated the imbalance of mitochondrial dynamics, and inhibited mitophagy and biosynthesis. BHD can maintain MQC homeostasis after CI through Cav-1 and improve CI injury. Discussion: Cav-1 can affect CI injury by regulating MQC, and this mechanism may be another target of BHD for anti-cerebral ischemia injury.

Predictive value of C-reactive protein, procalcitonin, and interleukin-6 on 30-day mortality in patients with bloodstream infections.

BACKGROUND: We aimed to assess the predictive performance of C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6) at different times points of bloodstream infections (BSI) management. METHODS: The cases were collected from January 2020 to June 2021 in the First Affiliated Hospital of Xinjiang Medical University (n=185). We collected patients' records of hsCRP, PCT, and IL-6 serum levels and calculated the clearance of these biomarkers on day 1, day 3, and day 5 (hsCRP-1, hsCRP-3, hsCRP-5, so do PCT, and IL-6). We analyzed these predictive performances for 30-day mortality with ROC and Logistic regression. The correlation between biomarkers and their clearance rates was performed by a rank correlation method. RESULTS: The 30-day mortality was 11.35% (21/185). Serial serum hsCRP-3, IL-6-3, PCT-1, PCT-3, and PCT-5 were statistically higher in BSI mortality than survivors. Significant predictive ability was found for 30-day mortality with blood culture (BC) reported fungi (OR, 0.033; 95% CI: 0.002-0.535) and PCT-5 (OR, 1.045; 95% CI: 1.013-1.078) levels, respectively. The AUC of PCT-5 levels for 30-day mortality was 0.784 (95% CI 0.678-0.949), and the cut-off value was 5.455ng/mL. CONCLUSIONS: PCT-5 is more valuable for the prognosis of 30-day mortality in patients with BSI compared to the other inflammatory biomarkers.

A UPLC-Q-TOF/MS and network pharmacology method to explore the mechanism of Anhua fuzhuan tea intervention in nonalcoholic fatty liver disease.

The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, etc. After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.

Apolipoprotein E knockout may affect cognitive function in D-galactose-induced aging mice through the gut microbiota-brain axis.

The gut microbiota plays an important role in central nervous system (CNS) disorders. Apolipoprotein E (ApoE) can affect the composition of the gut microbiota and is closely related to the CNS. However, the mechanism by which ApoE affects cognitive dysfunction through the gut microbiota-brain axis has thus far not been investigated. In this study, we used wild-type mice and ApoE knockout (ApoE-/-) mice to replicate the aging model and examined the effects of ApoE deletion on cognitive function, hippocampal ultrastructure, synaptophysin (SYP) and postsynaptic density 95 (PSD-95) in aging mice. We also explored whether ApoE deletion affects the gut microbiota and the metabolite profile of the hippocampus in aging mice and finally examined the effect of ApoE deletion on lipids and oxidative stress in aging mice. The results showed that the deletion of ApoE aggravated cognitive dysfunction, hippocampal synaptic ultrastructural damage and dysregulation of SYP and PSD-95 expression in aging mice. Furthermore, ApoE deletion reduced gut microbial makeup in aging mice. Further studies showed that ApoE deletion altered the hippocampal metabolic profile and aggravated dyslipidemia and oxidative stress in aging mice. In brief, our findings suggest that loss of ApoE alters the composition of the gut microbiota, which in turn may affect cognitive function in aging mice through the gut microbiota-brain axis.

Liuwei Dihuang Decoction Alleviates Cognitive Dysfunction in Mice With D-Galactose-Induced Aging by Regulating Lipid Metabolism and Oxidative Stress via the Microbiota-Gut-Brain Axis.

Background: Aging is an important cause of cognitive dysfunction. Liuwei Dihuang decoction (LW), a commonly applied Chinese medicine formula, is widely used for the treatment of aging-related diseases in China. Previously, LW was confirmed to be effective in prolonging life span and reducing oxidative stress in aged mice. Unfortunately, the underlying mechanism of LW remains unclear. The aim of this study was to interpret the mechanism by which LW alleviates cognitive dysfunction related to aging from the perspective of the microbiota-gut-brain axis. Method: All C57BL/6 mice (n = 60) were randomly divided into five groups: the control, model, vitamin E (positive control group), low-dose LW and high-dose LW groups (n = 12 in each group). Except for those in the control group, D-galactose was subcutaneously injected into mice in the other groups to induce the aging model. The antiaging effect of LW was evaluated by the water maze test, electron microscopy, 16S rRNA sequencing, combined LC-MS and GC-MS metabolomics, and ELISA. Results: Liuwei Dihuang decoction ameliorated cognitive dysfunction and hippocampal synaptic ultrastructure damage in aging mice. Moreover, LW decreased Proteobacteria abundance and increased gut microbiota diversity in aging mice. Metabolomic analysis showed that LW treatment was associated with the significantly differential abundance of 14 metabolites, which were mainly enriched in apelin signaling, sphingolipid metabolism, glycerophospholipid and other metabolic pathways. Additionally, LW affected lipid metabolism and oxidative stress in aging mice. Finally, we also found that LW-regulated microbial species such as Proteobacteria and Fibrobacterota had potential relationships with lipid metabolism, oxidative stress and hippocampal metabolites. Conclusion: In brief, LW improved cognitive function in aging mice by regulating lipid metabolism and oxidative stress through restoration of the homeostasis of the microbiota-gut-brain axis.

Epidemiological Survey on Echinococcosis in Xinjiang Uygur Autonomous Region, People's Republic of China.

BACKGROUND: According to the latest data, the detection rate of echinococcus in Hoboksar Mongol Autonomous County was 3.7%. The objective of this study is to further investigate the epidemiology of echinococcosis in Ho-boksar Mongol Autonomous County of Xinjiang Uygur Autonomous Region, People's Republic of China and provide the scientific evidence for preventive and control measures. METHODS: We performed ultrasound examination of 521 people in Hoboksar Mongol Autonomous County of Xinjiang Autonomous Region, and collected 508 serum samples, which were analyzed with enzyme-linked immunosorbent assay. Data were analyzed by t-test and multinomial logistic regression for risk factor analysis. We collected 126 pieces of herder's dog feces and used double antibody sandwich method to detect the positive rate of fecal antigen. RESULTS: The prevalence rate of human echinococcosis in this region was 4.4% (23/521), including 4.0% (21/521) for cystic echinococcosis (CE), 0.38% (2/521) for alveolar echinococcosis (AE). It was found that CE seropositivity was significantly different from gender, age, ethnic group, occupation, culture, area, income and awareness of this disease. The seroprevalence rate of people aged 41 - 65 (3.74%) was higher than of age 0 - 17 (0.197%) (p > 0.05); Female serological positive (4.921%) was higher than male (1.772%) (p > 0.005); Mongolian serological positive (5%) was higher than Han (0.197%) and Kazakhs (1.181%) (p > 0.05); The herdsmen serological positive (2.756% was higher than students (0.197%) (p > 0.05); The primary school students serological positive (2.559%) was higher than children before school 0% (p > 0.05); Chagankule serological positive (9.211%) was higher than Bayinaow (8.497%) (p > 0.05); The seroprevalence rate of people with income < 2,000 (3.74%) was higher than people with income over 5,000 (0.197%) (p > 0.05); The seroprevalence rate of people who had no disease awareness (4.724%) was higher than those who had awareness of Hydatid disease (1.969%) (p < 0.05). Multivariate logistic regression show age, ethic group and awareness of station are the influence factors of epidemiology of echinococcosis. Canine fecal antigen positive rate was 50% (p > 0.05). Narenhebuke (48.78%) was higher than chahet (20.00%), but there is no statistical difference (p > 0.05). CONCLUSIONS: The surveillance data and our study results tend to be consistent that echinococcosis has an increasing trend in Hoboksar Mongol Autonomous County. Efforts should be continued, in both animals and humans by increasing training campaigns and public awareness.

Fu brick tea alleviates high fat induced non-alcoholic fatty liver disease by remodeling the gut microbiota and liver metabolism.

Fu brick tea (FBT) and its extracts have good lipid-lowering effects and have been used in the treatment of obesity in previous studies. Unfortunately, the therapeutic effect of FBT on non-alcoholic fatty liver disease (NAFLD) has not been thoroughly studied. In this study, we explored the mechanism by which FBT alleviates NAFLD from the perspective of the gut microbiota and liver metabolites. The results showed that FBT could reduce the body weight, liver weight and abdominal fat of NAFLD mice, and improve liver pathological morphology, liver lipid deposition, blood lipids and liver function. Moreover, FBT improved the diversity of the gut microbiota and changed the profile of liver metabolism in NAFLD mice. Further studies showed that FBT could ameliorate the cecum barrier, and regulate the effects of factors related to lipid synthesis in the cecum and liver of NAFLD mice. In conclusion, the present study confirmed that FBT can alleviate high fat induced NAFLD by regulating the homeostasis of the gut microbiota and liver metabolites.

High Expression of Tim-3 in Alveolar Echinococcosis Mediates Depletion of CD8+ T Cell Function.

OBJECTIVE: CD8+ T cells can participate in immune action by secreting various cytokines, which have a killing effect on certain viruses, tumor cells, and other antigenic substances. However, in studies such as chronic viral infections and some parasitic infections, CD8+ T lymphocyte showed functional depletion, and its immune dysfunction was an important reason for the persistence of infection. Tim-3 has been shown to be a negative regulator of CD8+ T cell function, causing depletion of CD8+ T cells in cancer and chronic infection. However, the relationship between Tim-3 and CD8+ T cells in Echinococcus multilocularis infection is not clear. METHODS: In this study, we analyzed peripheral blood CD8+ T cells from 62 alveolar echinococcosis (AE) patients and 30 healthy controls. RESULTS: Compared with the healthy control group, the proportion of CD8+ T cells in the peripheral blood of AE patients increased significantly, while the levels of perforin, granzyme B and IFN-γ in peripheral blood CD8+ T cell related factors of metabolically active alveolar echinococcosis (MAAE) patients decreased significantly. Later detection revealed that the expression of Tim-3 on CD8+ T cells in the peripheral blood of MAAE patients was significantly higher than that of metabolically inactive alveolar echinococcosis (MIAE) patients and healthy controls. The expression levels of function-related factors perforin, granzyme B and IFN-γ in CD8+ Tim-3+ T cell were significantly lower in the CD8+Tim-3- T cells of AE patients. In vitro, the secretion of CD8+ T cell-associated factors was significantly restored by inhibiting Tim-3 expression. CONCLUSION: Therefore, the depletion of CD8+ T lymphocyte in patients with alveolar echinococcosis disease is considered to be related to the high expression of Tim-3 on the surface.

NT-pro BNP in AECOPD-PH: old biomarker, new insights-based on a large retrospective case-controlled study.

BACKGROUND: Pulmonary hypertension (PH) is one of the common complications in chronic obstructive pulmonary disease (COPD). The study aimed to evaluate the predicting ability of N-terminal pro brain natriuretic peptide (NT-pro BNP) in patients with AECOPD-PH and its relationship with the severity of PH. METHODS: A large retrospective case-controlled study (n = 1072) was performed in the First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2020, and patients were divided into stable COPD (n = 178), AECOPD (n = 688) and AECOPD-PH group (n = 206). Different statistical models were used to screen for reliable and stable biomarkers. RESULTS: In unadjusted analysis and PSM (model 1, 2, 3), red cell distribution width (RDW), total bilirubin (TBIL), and NT-pro BNP were higher in patients with AECOPD-PH than those in AECOPD group. Logistic regression analysis showed, when the range of NT-proBNP was 271-1165 pg/mL (OR: 0.293; 95%CI: 0.184-0.467; P < 0.001) and NT-proBNP > 1165 pg/mL (OR: 0.559; 95%CI: 0.338-0.926; P = 0.024), the morbidity risk of PH in AECOPD patients was increased, so did TBIL. In receiver operating characteristic (ROC) curves, at the cut-off value of NT-proBNP was 175.14 pg/mL, AUC was 0.651 (P < 0.001), which was better than TBIL (AUC: 0.590, P < 0.001). As for the results of rank correlation analysis, NT-proBNP had a weak correlation with severity of PH with AECOPD (rs = 0.299, P = 0.001) and its relative relevance with other biomarkers (RDW was 0.359 and TBIL was 0.238, P < 0.001). CONCLUSIONS: Our findings suggest that NT-proBNP has a diagnostic efficacy in AECOPD-PH and NT-proBNP has a weak correlation with severity of PH with AECOPD.

Clinical characteristics and chest computed tomography findings related to the infectivity of pulmonary tuberculosis.

AIM: This study mainly evaluates the clinical characteristics and chest chest computed tomography (CT) findings of AFB-positive and AFB-negative pulmonary tuberculosis (PTB) patients to explore the relationship between AFB-positive and clinico-radiological findings. METHODS: A retrospective analysis of 224 hospitalized tuberculosis patients from 2018 to 2020 was undertaken. According to the AFB smear results, they were divided into AFB-positive pulmonary tuberculosis (positive by Ziehl-Neelsen staining) and AFB-negative pulmonary tuberculosis and patients' CT results and laboratory test results were analyzed. RESULTS: A total of 224 PTB patients were enrolled. AFB-positive (n = 94, 42%) and AFB-negative (n = 130, 58%). AFB-positive patients had more consolidation (77.7% vs. 53.8%, p < 0.01), cavity (55.3% vs. 34.6%, p < 0.01), calcification (38.3% vs. 20%, p < 0.01), bronchiectasis (7.5% vs. 1.5%, p < 0.05), bronchiarctia (6.4% vs. 0.8%, p < 0.05), and right upper lobe involvement (57.5% vs. 33.1%, p < 0.01), left upper lobe involvement (46.8% vs. 33.1%, p < 0.05) and lymphadenopathy (58.5% vs. 37.7%, p < 0.01). CONCLUSION: The study found that when pulmonary tuberculosis patients have consolidation, cavity, upper lobe involvement and lymphadenopathy on chest CT images, they may have a higher risk of AFB-positive tuberculosis.

Clinical Significance of Procalcitonin, C-Reactive Protein, and Interleukin-6 in Helping Guide the Antibiotic Use for Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Currently, standards of antibiotic use in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients are controversial. OBJECTIVE: The aim of the present study was to analyze the value of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) levels to guide the antibiotic treatment of AECOPD patients. METHODS: A total of 371 patients with COPD or AECOPD were included in the study. Clinical and laboratory data were obtained at admission, 325 AECOPD patients and 46 sCOPD patients treated with antibiotics. The receiver operating curve (ROC) was used to evaluate the relationship between CRP, PCT, and IL-6. RESULTS: This study included medical record/case control 1, the COPD group (n = 46) and the AECOPD group (n = 325), and medical record control 2, the nonchanged antibiotic group (n = 203) and the changed antibiotic group (n = 61). In case 1, CRP, PCT, and IL-6 levels in the AECOPD group were higher than that in the control group (P < 0.05), while the result of ROC showed that IL-6 had higher AUC values (0.773) and higher sensitivity (71.7%) than other indicators. The specificity of PCT (93.5%) is higher than other indicators. In case 2, ROC curve results showed that the AUC value of IL-6 (0.771) was slightly higher than PCT and CRP. The sensitivity (85.2%) and specificity (65.5%) of CRP were higher than other indicators. CONCLUSIONS: IL-6 and PCT were elevated in AECOPD patients, resulting in a higher diagnostic value for AECOPD. CRP had a higher diagnostic value for antibiotic use in AECOPD patients.

Role of Cytokines on the Progression of Liver Fibrosis in Mice Infected with Echinococcus multilocularis.

BACKGROUND: Liver fibrosis is a significant pathological change of Echinococcus multilocularis (E. multilocularis) infection. This study aimed to explore the role of cytokines on the progression of liver fibrosis in mice infected with E. multilocularis. METHODS: Liver histopathological features at 2, 8, 30, 90 and 180 d were quantified by inflammatory severity score. The expression levels of inflammatory cytokines, fibrosis-related cytokines and hepatic cell apoptosis were measured using qRT-PCR and immunohistochemistry. RESULTS: At the early stage of infection, parasite stimulation triggers the rapid recruitment of immune cells, such as macrophages and neutrophils. These infiltrated immune cells then produce a large number of cytokines, such as iNOS (inducible nitric oxide synthase), a pro-inflammatory cytokine; TGF-ß (transforming growth factor) activated HSCs (hepatic stellate cells) to promote the proliferation of fibroblasts and secretion of ECM (extracellular matrix); MMP9 (matrix metalloproteinase 9) degraded basal ECM and facilitated its replacement by a highly dense interstitial matrix. At the middle and late stages of infection, the expression of IL-10 (interleukin-10) with general inhibitory effect was increased. The imbalance of fiber formation and degradation aggravated liver fibrosis. Meanwhile, the whole process of E. multilocularis infection was accompanied by the necrosis and apoptosis of hepatic cells. CONCLUSION: Along with the expansion of parasitic infection, dynamic changes in cytokine expression were observed on the liver fibrosis progression, which is helpful to provide some new ideas for the prevention and treatment of liver fibrosis in mice infected with E. multilocularis.

The diagnostic value of serum C-reactive protein, procalcitonin, interleukin-6 and lactate dehydrogenase in patients with severe acute pancreatitis.

OBJECTIVE: Acute pancreatitis (AP) is an inflammatory disease with rapid progression. In severe cases, it can cause systemic inflammatory response syndrome (SIRS), multiple organ failure (POF) and even death. The study aimed to investigate the diagnostic value of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6) and lactate dehydrogenase (LDH) in patients with severe AP. METHODS: AP patients (n = 153) divided into mild AP patients (n = 81) and severe AP patients (n = 72) were selected from June 2014 to June 2016. The demographic information (age, sex) and the hematological parameters (WBC, PLT, CRP, PCT, IL-6, LDH and so on) were analyzed. RESULTS: Significant differences were found out of CRP, PCT, IL-6 and LDH values between AP patients and controls (P < 0.05), even those results had significant difference between MAP group and SAP group (P < 0.05). In SAP group, the cut-off values of CRP, PCT, IL-6 and LDH were 16.62, 2.29, 16.66, 273.04; sensitivity 55.6%, 77.8%, 80.2%, 82.7%; specificity 73%, 94%, 85%, 96% and AUC 0.637, 0.929, 0.886, 0.919, respectively. The AUC of combined detection of CRP, PCT, IL-6 and LDH was 0.989 (95%CI). CONCLUSION: The combined detection of CRP, PCT, IL-6 and LDH has a high diagnostic value for judging the severity of AP.

Diagnostic value of hematological parameters in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disease with rapid onset and rapid progression. In severe cases, it can cause systemic inflammatory response syndrome (SIRS), multiple organ failure (POF) and death. In order to explore the effective index of early diagnosis of AP, we have detected the levels of serum lipase (LPS), serum amylase (S-AMY) and C-reactive protein (CRP). Meanwhile, cost evaluation was performed on these biochemical parameters for AP patients. METHODS: In this study, 212 patients were admitted with acute abdominal pain, divided into AP group (n=107) and non-AP group (n=105), including cholelithiasis (n=8), intestinal obstruction (n=34), acute cholangitis (n=14), acute cholecystitis (n=20), acute appendicitis (n=20) and pancreatic cancer (n=9). Demographic data and laboratory examination results were collected, the sensitivity and specificity of LPS, S-AMY and CRP in the diagnosis of AP were calculated respectively, as well as the costs of single or multiple tests were evaluated. RESULTS: The serum level of S-AMY and LPS in AP group were significantly higher than those in nonAP group (P<0.01), The serum level of CRP in AP group was higher than that in non-AP group (P<0.05). When the critical value of the normal reference value is three times as the critical value, the sensitivity and specificity of the LPS in diagnosing AP were 91.6% and 90.5%, S-AMY was 70.1% and 91.4%. And CRP was 59.8% and 56.2%, respectively. Compared with the trend of serum LPS expression, the expression trend of S-AMY was positively correlated (r=0.81), while there was no correlation with the trend of CRP expression. CONCLUSIONS: The ability of LPS to diagnose AP is significantly better than that of LPS + CRP, as well as the combined detection of LPS + CRP + S-AMY, which can be used as the first choice for laboratory examination of AP.

Kupffer Cells: Important Participant of Hepatic Alveolar Echinococcosis.

Aims: Kupffer cells (KCs) are the liver-resident macrophages and play a leading role in the regulation of liver homeostasis in physiological conditions and in pathology. The study aims to investigate the anti-echinococcosis effect of KCs and the effects of hepatic stellate cells (HSCs) activation in the progression of liver fibrosis in hepatic alveolar echinococcosis (hepatic AE). Methods: Hematoxylin-eosin (H&E) and Masson staining were used to assess the pathological inflammatory changes and collagen deposition, respectively. Immunohistochemistry and qRT-PCR were used to detect the number of aggregates of KCs, the expression of cytokines and activation of HSCs. Results: In the close group, H&E staining showed that the normal lobular structure was destroyed and inflammatory infiltration around the lesion could be observed, and Masson staining showed that blue collagen fibers were clearly deposited near the portal area. IHC showed that KCs surface markers CD68 and CD163, cytokine iNOS and Arg-1 were positively expressed in the vicinity of inflammatory lesions. qRT-PCR indicated that TNF-α, IL-10, and TGF-ß1 secreted by KCs were significantly higher than those in the distance group (P < 0.01). It is worth noticing that the expression levels of anti-inflammatory cytokines were slightly higher than that of pro-inflammatory cytokines. Both IHC and qRT-PCR results showed that HSCs activation markers, the expression of α-SMA and Desmin significantly increased. Conclusions: Our research indicates that KCs have immune-protective effect of anti-echinococcosis and promote liver fiber repair, and it also suggests that they have potential therapeutic value for patients with hepatic AE.